Cardiovascular disease is the most frequent cause of death in the United States. Selective arteriography is an important diagnostic tool in the diagnosis and management of patients with cardiovascular disease, but produces changes in the physiologic state and more serious side effects. The goal of the proposed work is to develop and test contrast media formulations, catheter designs and injection protocols for intra-arterial digital subtraction arteriography that will provide vessel opacification while minimizing side effects. Our long term goal is to develop IA-DSA procedures for quantitative measurements of blood flow, tissue perfusion and vessel mechanical properties. The project goal will be accomplished by (1) experiments in 5 canine arterial vascular beds and in vitro to determine the required contrast media concentration for good vascular visualization, (2) in vivo experiments to quantitatively describe the effects of contrast media osmolality and viscosity on hemodynamic and electrophysiologic alterations, and (3) in vivo and in vitro experiments to quantitatively describe the effects of injection protocols and catheter design on both downstream pressure (and flow) and the mixing of blood and contrast media. The results from (1), (2) and (3) will be used in the selection and development of formulations, catheter design and injection protocols for clinical testing. The accomplishment of the goal and specific aims of the proposed work will allow the development of intra-arterial DSA procedures that quantitatively measure cardiovascular hemodynamics and mechanics and also minimize the adverse effects caused by the selective injection of contrast media. One side benefit will be that the impact of the high cost of the new contrast media molecules can be mollified by reduction in concentrations and dose. our preliminary results strongly support the feasibility of the proposed work.